Spinal cord injuries are diseases that involve traumatic injuries, malpositions, fractures and so forth of the spine and that manifest lesions such as edema, minor hemorrhage and necrosis within the spinal cord to cause disorders in the movement of the four limbs, as well as in sensory functions, urinary elimination and so forth. The occurrence of spinal cord injuries is particularly frequent in the cervical segments and the thoracolumbar transition where the spinal cavity is narrow.
Most spinal cord injuries are traumatic and caused by traffic accidents, athletic accidents, falls and drops from heights, and so forth. They are known to occur, seldom though, as direct injury due to a puncturing needle, an injury to the femoral artery which results in a ischemic damage to regions it dominates, and as complications of high spinal anesthesia and peridural anesthesia that are caused by spinal cord compression and so forth due to the formation of hematoma in the peridural space.
Among the spinal cord injuries, those occurring in the upper cervical segments are often fatal since they cause quadriplegia and paralysis of the respiratory muscle; even if the patient survives, he is so seriously affected that he is paralyzed in all four limbs and must live his life under assisted respiration. The injury may be below the upper cervical segments but if it is a complete cord injury, flaccid paralysis of the four limbs below the level of the injury, a loss of sensory and reflex functions, as well as an extinction of urinating or defecating functions are occasionally immediate consequences. In an incomplete cord injury, the symptoms mentioned above may initially appear due to edema and a softening of the central part of the spinal cord but, the patient tends to recover from the injury in about 3-4 weeks, so it may well be described as less serious than the complete cord injury.
For the treatment of such spinal cord injuries, steroids have been known to be effective (see Spine, 19(20), 2281-2287, 1994; J. Spinal Disord., 5(1), 125-131, 1992; J. Neurosurg., 63(5), 703-713, 1985; JAMA, 251(1), 45-52, 1984, etc.) Among the steroids, dexamethasone and methylprednisolone administered in high doses are held to be effective in ameliorating the neurological symptoms of spinal cord injuries (J. Spinal Disord., 5(1), 125-131, 1992.).
Massive administration of steroids which is conventionally known to be effective against spinal cord injuries achieves the intended effect if it is done within 8 hours of their onset; on the other hand, it has been pointed out that in cases where steroids were administered after 8 hours of the onsent, the amelioration of the neurological symptoms was less than achievable in a spontaneous course of time.
In any event, the conventional therapeutic regimen using steroids has substantial difficulties associated with the side effects of massive administration and is not a very convenient practical approach. Therefore, it is desired to develop a drug that causes less side effects than the existing drugs and that yet is effective in the treatment of various spinal cord injuries.